Project Summary Gay and bisexual men (GBM) in the U.S. are burdened by a high and disproportionate rate of HIV infection and more than half of all HIV+ individuals are GBM. Improving viral load (VL) suppression is associated with a significant reduction in the sexual transmission of HIV. Moreover, research is needed to better understand the modifiable social and behavioral factors that influence their long-term health. Chronic experiences of sexual minority stressors (e.g., internalized homonegativity) have been shown to influence a variety of mental, behavioral, and physical health outcomes for GBM, including general stress (e.g., cortisol) and immune (e.g., cytokines) outcomes, as well as HIV-specific health outcomes (e.g., CD4 count) among HIV+ GBM. Chronic experiences of HIV-related stressors have also been shown to impact mental health and health behaviors for HIV+ GBM, though there is substantially less research on their role in the health of HIV+ GBM. Previous research, including our own, has shown that fluctuations in sexual minority and HIV-specific stressors (i.e., acute experiences of these stressors) are measurable and meaningfully associated with health outcomes. Both HIV infection and substance use are associated with declines in neurocognitive function and emerging evidence suggests that emotional processing may help explain the impact of psychological phenomena on health outcomes. To develop interventions that are robust and durable, research is needed that examines the unique and overlapping influence of sexual minority and HIV-related stressors on health outcomes for HIV+ GBM within a unified biopsychosocial model. Such a model should take into account both individual-level (i.e., chronic) and situational (i.e., acute) experiences of these stressors to examine their independent associations with health, and should consider whether emotional interference in cognitive processing might moderate these associations. Aim 1 of the study is to test a biopsychosocial model of sexual minority and HIV-related stress and health, examining direct and indirect effects of these stressors on each outcome. Aim 2 is to test the moderating role of emotional interference in cognitive processing on these associations. Finally, Aim 3 is to examine the extent of intraindividual variability over one year in sexual minority and HIV-related stressors, VL, CD4, and cytokines. Although not an aim, the study will culminate in the development of guidelines for future intervention development and we will gather participant feedback on these recommendations. To accomplish these aims, we will enroll 250 HIV+ GBM and follow them for 12 months. We will use ecological momentary assessment (EMA) for 21 days and quarterly longitudinal follow-ups over one year to test the impact of sexual minority and HIV-related stress on physiological stress (diurnal cortisol) and long-term immune outcomes (VL suppression, CD4 count, cytokines). This study will address novel questions about the relative role of sexual minority and HIV-related stress in the health of HIV+ GBM to guide the development of interventions to improve health and reduce HIV transmission, morbidity, and mortality among HIV+ GBM.